The recent finding of a family in the Netherlands with a documented X- linked deficiency of monoamine oxidase A (MAOA)associated with episodic violent behavior (Brunner et al, 1993) has prompted us to evaluate the frequency of this deficiency state in males. We plan to undertake a genetic screen for mutations in the MAOA gene in adult males with a history of episodic impulsive or violent behavior, as compared to control males and males with undiagnosed X-linked mental retardation, Parkinson disease or hypertension DNA from blood samples will be obtained from several hundred affected individuals whose family history is consistent with X-linked mode of transmission of an episodic impulsive behavioral disorder. When possible blood samples will also be analyzed for altered amine metabolites by our collaborator, Dr. Dennis Murphy (NIMH), in which cases only individuals with abnormal levels of amines will be analyzed genetically. The integrity of the entire coding region of the MAOA gene will be determined by amplification of all 15 exons, using the polymerase chain reaction (PCR)and primers in the intronic and untranslated regions. Amplified fragments 150-250 kb in size will be analyzed for single strand conformational "polymorphisms" (SSCP)by resolution on non-denaturing acrylamide gels. Altered fragments will be sequenced directly to resolve sequence variations. This pilot study will provide an estimate of the frequency of the MAOA deficiency state as a basis for future investigations of this syndrome and the phenotypes associated with it.